Proteases are known to be subject to degradation by autolysis since these enzymes contain the same chemical bonds which are cleaved by proteolytic activity. However, it was generally believed that such degradation was generalized, yielding many random small fragments.
EP application 0130756 suggests improving the properties of alkaline proteases by site directed mutagenesis, including oxidative stability, pH activity profiles, K.sub.m, k.sub.cat, k.sub.cat /K.sub.m ratios and substrate specificity. However, no mention is made of altering the stability of such proteases to autolytic cleavage.
WO 87/04461 discloses a method of producing thermally stable and pH stable subtilisin analogs by replacing Asn-Gly sequences in subtilisins.